Rethinking the role of phosducin: Light-regulated binding of phosducin to 14-3-3 in rod inner segments

Phosducin (Pd), a small protein found abundantly in photoreceptors, is wide ly assumed to regulate light sensitivity in the rod outer segment through i nteraction with the heterotrimeric G protein transducin. But, based on hist ochemistry and Western blot analysis, Pd is found almost entirely in the in ner segment in both light and dark, most abundantly near the rod synapse. W e report a second small protein, 14-3-3, in the rod with a similar distribu tion. By immunoprecipitation, phospho-Pd is found to interact with 14-3-3 i n material from dark-adapted retina, and this interaction is markedly dimin ished by light, which dephosphorylates Pd. Conversely, unphosphorylated Pd binds to inner segment C protein(s) in the light. From these results and re ported functions of 14-3-3, we have constructed a hypothesis for the regula tion of light sensitivity at the level of rod synapse. By dissociating the Pd/14-3-3 complex, light enables both proteins to function in this role.